title: Preparation of pH-responsive polymer core-shell nanospheres for delivery of hydrophobic antineoplastic drug ellipticine.
abstract: Antineoplastic drug ellipticine and its derivatives are used in human cancer therapy. However, their clinical applications have been limited by its great hydrophobicity and severe side effects. An efficient delivery system is therefore very desirable. In this research, an ellipticine-loaded core-shell structured nanosphere namely poly(DEAEMA)-poly(PEGMA) is designed as a drug carrier and prepared via a two-step semibatch emulsion polymerization method where DEAEMA and PEGMA represent 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol) methacrylate, respectively. The in-vitro release profiles of ellipticine towards the different pH liposome vesicles are recorded as a function of time at 37 °C. It is found that release of ellipticine from the core-shell polymer matrix is a pH-responsive and controlled release process. The three pH's of 3, 4, and 5 trigger a significant ellipticine release of 88% after 98 h, 83% after 98 h, and 79% after 122 h, respectively. The release mechanism of ellipticine from the core-shell polymer matrix under acidic conditions is explored. The synthesis and encapsulation process developed herein provides a new perspective for the development of appropriate delivery systems to deliver the ellipticine and its analogues, as well as other types of hydrophobic drugs to a given target cell or tumor tissue.
authors.affiliation: Department of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON, Canada, N2L 3G1. h54wang@uwaterloo.ca.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Garry L
authors.initials: GL
authors.lastname: Rempel
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D060326:Chemistry Techniques, Synthetic; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004611:Ellipticines / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008689:Methacrylates; D046529:Microscopy, Electron, Transmission; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004611:Ellipticines; D008081:Liposomes; D008689:Methacrylates; C524499:polyethylene glycol methacrylate; C034192:ellipticine; D011092:Polyethylene Glycols
keywords: core-shell polymers; drug delivery; ellipticine; nanospheres; pH-responsive